Open Access. Powered by Scholars. Published by Universities.®

Chemicals and Drugs Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 3 of 3

Full-Text Articles in Chemicals and Drugs

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang Aug 2013

Identification Of A Human Monoclonal Antibody To Replace Equine Diphtheria Anti-Toxin For The Treatment Of Diphtheria, Leila M. Sevigny, Brian J. Booth, Kirk J. Rowley, Brett A. Leav, Peter S. Cheslock, Kerry A. Garrity, Susan Sloan, Gregory J. Babcock, William D. Thomas, Mark Klempner, Yang Wang

William D Thomas Jr

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of …


Structural Basis For Enzyme I Inhibition By Α-Ketoglutarate, Vincenzo Venditti, Rodolfo Ghirlando, G. Marius Clore Jan 2013

Structural Basis For Enzyme I Inhibition By Α-Ketoglutarate, Vincenzo Venditti, Rodolfo Ghirlando, G. Marius Clore

Vincenzo Venditti

Creating new bacterial strains in which carbon and nitrogen metabolism are uncoupled is potentially very useful for optimizing yields of microbial produced chemicals from renewable carbon sources. However, the mechanisms that balance carbon and nitrogen consumption in bacteria are poorly understood. Recently, α-ketoglutarate (αKG), the carbon substrate for ammonia assimilation, has been observed to inhibit Escherichia coli enzyme I (EI), the first component of the bacterial phosphotransferase system (PTS), thereby providing a direct biochemical link between central carbon and nitrogen metabolism. Here we investigate the EI-αKG interaction by NMR and enzymatic assays. We show that αKG binds with a KD …


Structure, Dynamics And Biophysics Of The Cytoplasmic Protein–Protein Complexes Of The Bacterial Phosphoenolpyruvate: Sugar Phosphotransferase System, Vincenzo Venditti Jan 2013

Structure, Dynamics And Biophysics Of The Cytoplasmic Protein–Protein Complexes Of The Bacterial Phosphoenolpyruvate: Sugar Phosphotransferase System, Vincenzo Venditti

Vincenzo Venditti

The bacterial phosphotransferase system (PTS) couples phosphoryl transfer, via a series of bimolecular protein–protein interactions, to sugar transport across the membrane. The multitude of complexes in the PTS provides a paradigm for studying protein interactions, and for understanding how the same binding surface can specifically recognize a diverse array of targets. Fifteen years of work aimed at solving the solution structures of all soluble protein–protein complexes of the PTS has served as a test bed for developing NMR and integrated hybrid approaches to study larger complexes in solution and to probe transient, spectroscopically invisible states, including encounter complexes. We review …